This invention relates to methods for inhibiting sex steroid formation and in particular to novel methods for inhibiting androgen and estrogen formation in vivo in warm-blooded animals, including humans.
For a number of years, there has been research for compounds which can efficiently inhibit androgen and/or estrogen formation (e.g. enzyme inhibitors) or for compounds which may suppress androgen or estrogen action (steroid antagonists), without casuign adverse effects to healthy tissues.
Recently, estradiol derivatives bearing a carboxyalkyl substituent at the 7.alpha.-position maintained their affinity for the estrogen receptor when linked via their carboxy group to agarose or polyacrylamide resin for affinity chromatography purification of the estrogen receptor (Bucourt et al., J. Biol. Chem. 253: 8221, 1978). It was subsequently found that certain 7.alpha.-substituted derivatives of estradiol possess antiestrogenic activity (Bowler et al., 1985, Eur, Patent Application 0138504; Wakeling and Bowler, J. Steroid Biochem. 30: 141-147, 1989).
Non steroidal compounds bearing a similar aliphatic side chain have also been found to possess antiestrogenic activity (U.S. Pat. No. 4,732,912).
Some steriod derivative, such as especially 16-methylene estradiol and 16-methylene estrone, have been described as inhibitors of 17.alpha.-hydroxysteroid dehydrogenase activity (Thomas et al., J. Biol. Chem. 258: 11500, 1983).
Prior art methods have not been completely effective in inhibiting sex steriod synthesis while avoiding undesirable side effects.